New Sulfoxide-Containing Derivatives from the Resin of Ferula sinkiangensis

Abstract

Four undescribed sulfoxide-containing derivatives, sinkiangenoxides A and B, (2Z, 4E)-sinkiangenoxide C, and (2E, 4E)-sinkiangenoxide C (1 – 4), and one known compound, 1-(methylthio)propyl (E)-1-propenyl disulfide (5), were isolated from the resin of Ferula sinkiangensis. Their structures were determined based on spectroscopic methods, including IR, UV, HRESIMS, NMR, and CD analysis. Compounds 2 – 4 showed moderate cytotoxic activities against four human cancer cell lines with IC₅₀ values ranging from 15.0 to 40.3 µM. Sinkiangenoxide B (2) was shown to induce apoptosis in HepG2 cells. In addition, compound 5 effectively attenuated lipopolysaccharide-induced nitric oxide release and TNF-α, IL-1β, IL-6, and IL-10 expression.

Key words

Ferula sinkiangensis - Apiaceae - sulfoxide - structural elucidation - cytotoxic - NO release

• References

• 1 El-Aasr M, Fujiwara Y, Takeya M, Ono M, Nakano D, Okawa M, Kinjo J, Ikeda T, Miyashita H, Yoshimitsu H, Nohara T. Garlicnin A from the fraction regulating macrophage activation of Allium sativum . Chem Pharm Bull (Tokyo) 2011; 59: 1340-1343
• 2 Nohara T, Kiyota Y, Sakamoto T, Manabe H, Ono M, Ikeda T, Fujiwara Y, Nakano D, Kinjo J. Garlicnins B₁, C₁, and D, from the fraction regulating macrophage activation of Allium sativum . Chem Pharm Bull (Tokyo) 2012; 60: 747-751
• 3 Nohara T, Fujiwara Y, Ikeda T, Murakami K, Ono M, Nakano D, Kinjo J. Cyclic sulfoxides garlicnins B₂, B₃, B4, C₂, and C₃ from Allium sativum . Chem Pharm Bull (Tokyo) 2013; 61: 695-699
• 4 Nohara T, Fujiwara Y, Ikeda T, Yamaguchi K, Manabe H, Murakami K, Ono M, Nakano D, Kinjo J. Acyclic sulfides, garlicnins L-1–L-4, E, and F, from Allium sativum . Chem Pharm Bull (Tokyo) 2014; 62: 477-482
• 5 Nohara T, Fujiwara Y, Kudo R, Yamaguchi K, Ikeda T, Murakami K, Ono M, Kajimoto T, Takeya M. Isolation and characterization of new onionins A₂ and A₃ from Allium cepa, and of onionins A₁, A₂, and A₃ from Allium fistulosum . Chem Pharm Bull (Tokyo) 2014; 62: 1141-1145
• 6 Nohara T, Fujiwara Y, Komota Y, Kondo Y, Saku T, Yamaguchi K, Komohara Y, Takeya M. Cyclic sulfoxides-garlicnins K₁, K₂, and H₁-extracted from Allium sativum . Chem Pharm Bull (Tokyo) 2015; 63: 117-121
• 7 El-Aasr M, Fujiwara Y, Takeya M, Ikeda T, Tsukamoto S, Ono M, Nakano D, Okawa M, Kinjo J, Yoshimitsu H, Nohara T. Onionin A from Allium cepa inhibits macrophage activation. J Nat Prod 2010; 73: 1306-1308
• 8 Nohara T, Fujiwara Y, Ikeda T, Murakami K, Ono M, El-Aasr M, Nakano D, Kinjo J. Two new bicyclic sulfoxides from Welsh onion. J Nat Med 2016; 70: 260-265
• 9 Hamada T, Matsunaga S, Yano G, Fusetani N. Polytheonamides A and B, highly cytotoxic, linear polypeptides with unprecedented structural features, from the marine sponge, Theonella swinhoei . J Am Chem Soc 2005; 127: 110-118
• 10 Thornburg CC, Cowley ES, Sikorska J, Shaala LA, Ishmael JE, Youssef DT, McPhail KL. Apratoxin H and apratoxin A sulfoxide from the Red Sea cyanobacterium Moorea producens . J Nat Prod 2013; 76: 1781-1788
• 11 Suzuki T, Kubota T, Kobayashi J. Eudistomidins H–K, new β-carboline alkaloids from the Okinawan marine tunicate Eudistoma glaucus . Bioorg Med Chem Lett 2011; 21: 4220-4223
• 12 Makarieva TN, Stonik VA, Dmitrenok AS, Grebnev BB, Isakov VV, Rebachyk NM, Rashkes YW. Varacin and three new marine antimicrobial polysulfides from the far-eastern ascidian Polycitor sp. J Nat Prod 1995; 58: 254-258
• 13 Aiello A, Fattorusso E, Imperatore C, Luciano P, Menna M, Vitalone R. Aplisulfamines, new sulfoxide-containing metabolites from an Aplidium tunicate: absolute stereochemistry at chiral sulfur and carbon atoms assigned through an original combination of spectroscopic and computational methods. Mar Drugs 2012; 10: 51-63
• 14 Marzuka A, Huang L, Theodosakis N, Bosenberg M. Melanoma treatments: advances and mechanisms. J Cell Physiol 2015; 230: 2626-2633
• 15 Su J. Dictionary of Chinese traditional Medicines. Shanghai: Shanghai Peopleʼs Press; 1998
• 16 Eigner D, Scholz D. Ferula asa-foetida and Curcuma longa in traditional medical treatment and diet in Nepal. J Ethnopharmacol 1999; 67: 1-6
• 17 Afifi FU, Abu-Irmaileh B. Herbal medicine in Jordan with special emphasis on less commonly used medicinal herbs. J Ethnopharmacol 2000; 72: 101-110
• 18 Samsam-Shariat H. Collection of medicinal Herbs. Tehran: Mani Publications; 2007
• 19 Li GZ, Wang JC, Li XJ, Cao L, Gao L, Lv N, Si JY. An unusual sesquiterpene coumarin from the seeds of Ferula sinkiangensis . J Asian Nat Prod Res 2016; 18: 891-896
• 20 Rashidi M, Khalilnezhad A, Amani D, Jamshidi H, Muhammadnejad A, Bazi A, Ziai SA. Umbelliprenin shows antitumor, antiangiogenesis, antimetastatic, anti-inflammatory, and immunostimulatory activities in 4T1 tumor-bearing Balb/c mice. J Cell Physiol 2018; 233: 8908-8918
• 21 Bashir S, Alam M, Adhikari A, Shrestha RL, Yousuf S, Ahmad B, Parveen S, Aman A, Iqbal Choudhary M. New antileishmanial sesquiterpene coumarins from Ferula narthex Boiss. Phytochem Lett 2014; 9: 46-50
• 22 Liang T, Ma GZ, Li L, Ma LY, Xu XQ. Karatavicinol A, a new anti-ulcer sesquiterpene coumarin from Ferula sinkiangensis . Chem Nat Comp 2013; 49: 606-609
• 23 Chandran S, Sakthivel M, Thirumavalavan M, Thota JR, Mariappanadar V, Raman P. A facile approach to the isolation of proteins in Ferula asafoetida and their enzyme stabilizing, anti-microbial and anti-oxidant activity. Int J Biol Macromol 2017; 102: 1211-1219
• 24 Bagheri SM, Sahebkar A, Gohari AR, Saeidnia S, Malmir M, Iranshahi M. Evaluation of cytotoxicity and anticonvulsant activity of some Iranian medicinal Ferula species. Pharm Biol 2010; 48: 242-246
• 25 Latifi E, Mohammadpour AA, Fathi HB, Nourani H. Antidiabetic and antihyperlipidemic effects of ethanolic Ferula assa-foetida oleo-gum-resin extract in streptozotocin-induced diabetic wistar rats. Biomed Pharmacother 2019; 110: 197-202
• 26 Osman AMG, Abourashed EA, Slade D, Ahmed SA, Gul W, Khan SI, Elfadl TA, Dale OR, Husni AS, Cutler SJ, ElSohly MA. Synthesis and in vitro evaluation of ferutinol aryl esters for estrogenic activity and affinity toward cannabinoid receptors. Med Chem Res 2015; 24: 2670-2678
• 27 Dastan D, Salehi P, Ghanati F, Gohari AR, Maroofi H, Alnajar N. Phytotoxicity and cytotoxicity of disesquiterpene and sesquiterpene coumarins from Ferula pseudalliacea . Ind Crop Prod 2014; 55: 43-48
• 28 Li N, Guo TT, Zhou D. Bioactive Sesquiterpene Coumarins from Plants. In: Atta-ur R. ed. Studies in natural Products Chemistry. Amsterdam: Elsevier; 2018: 251-282
• 29 Iranshahi M, Amin GR, Amini M, Shafiee A. Sulfur containing derivatives from Ferula persica var. latisecta . Phytochemistry 2003; 63: 965-966
• 30 Duan H, Takaishi Y, Tori M, Takaoka S, Honda G, Ito M, Takeda Y, Kodzhimatov OK, Kodzhimatov K, Ashurmetov O. Polysulfide derivatives from Ferula foetida . J Nat Prod 2002; 65: 1667-1669
• 31 Yousefi M, Mohammadi M, Habibi Z, Shafiee A. New polysulphanes from aerial parts of Ferula behboudiana Rech. f. & Esfand. Nat Prod Res 2010; 24: 1352-1357
• 32 Mirjani R, Shahverdi AR, Iranshahi M, Amin G, Shafiee A. Identification of antifungal compounds from Ferula persica. var. persica . Pharm Biol 2005; 43: 293-295
• 33 Iranshahi M, Noroozi S, Behravan J, Karimi G, Schneider B. Persicasulphide C, a new sulphur-containing derivative from Ferula persica . Nat Prod Res 2009; 23: 1584-1588
• 34 Soltani S, Amin GR, Salehi-Sourmaghi MH, Schneider B, Lorenz S, Iranshahi M. Sulfur-containing compounds from the roots of Ferula latisecta and their cytotoxic activities. Fitoterapia 2018; 124: 108-112
• 35 Chitsazian-Yazdi M, Agnolet S, Lorenz S, Schneider B, Esʼhaghi Z, Kasaian J, Khameneh B, Iranshahi M. Foetithiophenes C–F, thiophene derivatives from the roots of Ferula foetida . Pharm Biol 2015; 53: 710-714
• 36 Yang JR, An Z, Li ZH, Jing S, Qin HL. Sesquiterpene coumarins from the roots of Ferula sinkiangensis and Ferula teterrima . Chem Pharm Bull 2006; 54: 1595-1598
• 37 Xing YC, Li N, Zhou D, Chen G, Jiao K, Wang W, Si Y, Hou Y. Sesquiterpene coumarins from Ferula sinkiangensis act as neuroinflammation inhibitors. Planta Med 2017; 83: 135-142
• 38 Wang JC, Gao Y, Wang H, Chen L, Cao L, Xu J, Li X, Zhao Y, Zhu J, Si J. Apoptosis induction and cell cycle arrest induced by Sinkiangenone B, a novel phenylpropanoid derivative from the resin of Ferula sinkiangensis K. M. Shen. RSC Adv 2018; 8: 4093-4103
• 39 Block E, Gulati H, Putman D, Sha D, You N, Zhao SH. Allium chemistry: synthesis of 1-[alk(en)ylsulfinyl]propyl alk(en)yl disulfides (Cepaenes), antithrombotic flavorants from homogenates of onion (Allium cepa). J Agric Food Chem 1997; 45: 4414-4422
• 40 Berardozzi R, Guido CA, Capozzi MAM, Cardellicchio C, Di Bari L, Pescitelli G. Circular dichroism and TDDFT investigation of chiral fluorinated aryl benzyl sulfoxides. Eur J Org Chem 2015; 2015: 5554-5562
• 41 Pai VG, Pai NV, Thacker HP, Shinde JK, Mandora VP, Erram SS. Comparative clinical trial of S-pantoprazole versus racemic pantoprazole in the treatment of gastro-esophageal reflux disease. World J Gastroenterol 2006; 12: 6017-6020
• 42 Di Bari L, Pescitelli G, Pratelli C, Pini D, Salvadori P. Determination of absolute configuration of acyclic 1,2-Diols with Mo₂(OAc)₄. 1. Snatzkeʼs method revisited. J Org Chem 2001; 66: 4819-4825
• 43 Liu J, Liu Y, Si Y, Yu S, Qu J, Xu S, Hu Y, Ma S. New vernocuminosides from the stem barks of Vernonia cumingiana Benth. Steroids 2009; 74: 51-61
• 44 Xiang W, Zhang RJ, Jin GL, Tian L, Cheng F, Wang JZ, Xing XF, Xi W, Tang SJ, Chen JF. RCE-4, a potential anti-cervical cancer drug isolated from Reineckia carnea, induces autophagy via the dual blockade of PI3K and ERK pathways in cervical cancer CaSki cells. Int J Mol Med 2020; 45: 245-254
• 45 Yue L, Ailin W, Jinwei Z, Leng L, Jianan W, Li L, Haiming C, Ling H, Chuanjian L. PSORI-CM02 ameliorates psoriasis in vivo and in vitro by inducing autophagy via inhibition of the PI3K/Akt/mTOR pathway. Phytomedicine 2019; 64: 153054
• 46 Wang L, Oh JY, Jayawardena TU, Jeon YJ, Ryu B. Anti-inflammatory and anti-melanogenesis activities of sulfated polysaccharides isolated from Hizikia fusiforme: Short communication. Int J Biol Macromol 2020; 142: 545-550